Você está na página 1de 149

Definite case of

TB:

A patient with M. tuberculosis (MTB)


complex identified from a clinical
specimen, either by culture or by a newer
method such as molecular line probe
assay
In countries that lack the laboratory
capacity to routinely identify MTB, a
pulmonary case with one or more initial
sputum smear examinations positive for
acidfast bacilli

Extrapulmonary
tuberculosis
(EPTB):
Tuberculosis can involve any organ system in the body.
While pulmonary tuberculosis is the most common
presentation, extrapulmonary tuberculosis (EPTB) is
also an important clinical problem.
Extrapulmonary tuberculosis (EPTB):
Isolated occurrence of TB at body sites other than the
lung
Extrapulmonary tuberculosis (EPTB) diagnosis:
At least one specimen with confirmed M. tuberculosis or
histological or strong clinical evidence consistent with
active EPTB
Case definition of an EPTB case with several sites
affected depends on: the site representing the most
severe form of disease

Pathogenesis:

Manifestations of EPTB:

EPTB involves organs other than the lungs:


Pleura
Lymph nodes
Abdomen
Genitourinary
Skin
Joints and bones
Meninges and brain
Other: skin, eye

Distribution of TB cases:
Distribution of tuberculosis cases by
anatomical site in HIV-negative patients

Distribution of tuberculosis cases by


anatomical site in HIV-positive patients

In immunocompetent adults,
it has been observed that
EPTB constituted about 15 to
20 per cent of all cases of
TB.
In HIV-positive patients, EPTB
accounts for more than 50
per cent of all cases of TB.

Presentation:
constitutional symptoms such as fever,
anorexia, weight loss, malaise and fatigue.
In India patients with EPTB especially when
the disease is located at an obscure site,
may present with pyrexia of unknown
origin (PUO) and this may be the only
diagnostic clue in them.
symptoms and signs related to the organ
system involved and these are discussed
under the respective anatomic sites.

Lymph node
tuberculosis

Lymph node
tuberculosis
Historically, lymph node tuberculosis (LNTB)

has been called the Kings evil referring to the


divine benediction which was presumed to be
the treatment for it. It was also referred to as
scrofula meaning glandular swelling (Latin)
and full necked sow (French).
Peripheral lymph nodes are most often affected
and cervical involvement is the most.
In India and other developing countries LNTB
continues to be the most common form of EPTB
and lymphadenitis due to non-tuberculous
mycobacteria (NTM) is seldom seen. On the
other hand, NTM are the most common cause

Pathogenesis:
1. LNTB is considered to be the local manifestation of a
systemic disease whereas NTM lymphadenitis is thought to
be a truly localised disease.
. M. tuberculosis gains entry into the body via the respiratory
tract and undergoes haematogenous and lymphatic
dissemination.
. Hilar and mediastinal lymph nodes are initially involved.
. This may occur at the time of primary infection or may
occur later in life due to reinfection or reactivation of
previous infection. Sometimes, tonsil is an important portal
of entry.
2. In contrast NTM, gain entry into the lymph nodes directly
via oropharyngeal mucosa, salivary glands, tonsils, gingiva
or conjunctiva, and lymph node involvement represents a
localised disease.

The infection then spreads via the lymphatics


to the draining cervical lymph nodes.
Initially, the nodes are discrete. Periadenitis
results in matting and fixation of the lymph
nodes.
The lymph nodes coalesce and break down
due to formation of caseous pus.
This may perforate the deep fascia and
present as a collar-stud abscess. Overlying skin
becomes indurated and breaks down, resulting
in sinus formation which may remain unhealed
for years.
Healing may occur from each of the stages
with calcification and scarring.

Clinical presentation:

LNTB often affects children and young adults.


Patients usually present with slowly enlarging lymph nodes and
may otherwise be asymptomatic.
In HIV-negative patients, isolated cervical lymphadenopathy is
most often seen in about two-thirds of the patients. among HIVnegative as well as HIV-positive patients, cervical lymph nodes
were most commonly affected followed by axillary and inguinal
lymph nodes.
Multifocal involvement was observed in 39 and 90 per cent among
HIV-negative and HIV-positive patients respectively. In HIVpositive
patients, multifocal involvement, intrathoracic and intraabdominal
lymphadenopathy and associated pulmonary disease are more
common.
May present with constitutional symptoms of: fever, weight loss,
fatigue and occasionally night sweats. Patients with mediastinal
lymphadenopathy may present with cough and dysphagia.

Physical findings depend upon the stage of the


disease. The enlarged lymph nodes may be of varying size, are
usually firm and may be discrete or matted. If necrosis and abscess
formation have taken place they may become cystic in consistency.
The lymph nodes are usually not tender unless secondary bacterial
infection has occurred. Physical examination may be unremarkable
but for palpable lymphadenopathy.
Occasionally, lymph node abscess may burst leading to a chronic nonhealing sinus and ulcer formation. Classically, tuberculosis sinuses
have thin, bluish, undermined edges with scanty watery discharge.

Upper abdominal and mediastinal lymph nodes


may cause: (pressure symptoms mostly)
o Thoracic duct obstruction and chylothorax, chylous ascites or chyluria.
o Rarely, biliary obstruction due to enlarged lymph nodes can result in
obstructive jaundice.
o Cardiac tamponade has also been reported due to mediastinal lymph
node tuberculosis.
o Uncommon manifestations observed in patients with mediastinal
lymph node involvement include dysphagia, cough,
oesophagomediastinal fistula, and tracheo-oesophageal fistula.

Peripheral tuberculosis lymphadenopathy


has been classified into five stages: These
include:
(i) stage 1, enlarged, firm mobile discrete
nodes showing non-specific reactive
hyperplasia;
(ii) stage 2, large rubbery nodes fixed to
surrounding tissue owing to periadenitis;
(iii) stage 3, central softening due to
abscess formation;
(iv) stage 4, collar-stud abscess formation;
and
(v) stage 5, sinus tract formation.

Tubercular lymphadenopathy
stages:
Stage 1-2 and 3

Stage 4 and 5

Diagnosis:
1. FNA: smear microscopy, TB
culture, histology,

2. GeneXpert
3. Radiological findings
.CT scan (for intrathoracic and
intraabdominal LN)
.CXR

Differential diagnosis:
D/D: In severely immunocompromised
patients, tuberculous lymphadenopathy
may be acute and resemble acute
pyogenic lymphadenitis.
In adults, the differential diagnosis of
tuberculous lymphadenopathy includes the
following: persistent generalized
lymphadenopathy (PGL), lymphoma, Kaposi
sarcoma, carcinomatous metastases,
sarcoid, and drug reactions (e.g. phenytoin).

Persistent generalized
lymphadenopathy (PGL):
PGL is a feature of HIV infection which develops in up
to 50% of HIVinfected individuals. It is of no
prognostic significance.There is no specific treatment.
The diagnostic criteria for PGL are as follows: lymph
nodes larger than
1 cm in diameter
in 2 or more extra-inguinal sites
for 3 or more months.
The nodes are non-tender, symmetrical, and often
involve the posterior cervical and epitrochlear nodes.
PGL may slowly regress during the course of HIV
infection and may disappear before the onset of AIDS.

The features of lymph nodes that indicate a


need for further investigation, including
biopsy, are:
large (> 4 cm diameter) or rapidly growing
lymph nodes
asymmetrical lymphadenopathy
tender/painful lymph nodes not associated
with local infection
matted/fluctuant lymph nodes
obvious constitutional features (e.g. fever,
night sweats, weight loss)
hilar or mediastinal lymphadenopathy on
CXR.

Pleural TB:
Manifest as Pleural effusion or
empyema thoracis
Tuberculosis pleural effusion is
categorised as extrapulmonary
despite an intimate anatomic
relationship between pleura and
the lungs.

Pathogenesis:
Small subpleural focus ruptures into the pleural
space leads to Interaction between tubercle bacilli or
their specific components inducing a delayed
hypersensitivity reaction. (evidence suggests that
patients with TB pleural effusion have significantly
higher levels of IFN-Y in the pleural fluid as compared
to peripehral blood thus exhibiting localisation of
predominantly Th1-type immunity in the pleural
fluid)
Rupture of a cavity (with caseous material) into the
pleural space results in empyema thoracis.
Less often, rupture of caseous paratracheal lymph
nodes, paravertebral abscess or osteomyelitis of the
ribs can result in empyema thoracis.

Clinical Features:

Acute illness, symptoms for few days weeks


Pleuritic chest pain
Nonproductive cough
Dyspnoea
Fever
Constitutional symptoms like wt loss, loss of
appetite
Empyema thoracic may present with cough
with expectoration, fever, and toxaemia.
Anaemia and hypoproteinaemia are often
present.

Physical Examination:

Digital clubbing
Decreased air entry
Dull percussion of chest
Friction rub
Intercostal tenderness
Occasionally, tuberculosis empyema
may present as a chest wall mass or
draining sinus tract (tuberculosis
empyema necessitatis).

Diagnosis:

Imaging (CXR, sonar, CTscan)


Pleural tap
Differential white cell counts
Total protein, LDH, glucose
Adenosine deaminase (ADA)
Smear microscopy, TB culture
(GeneXpert)
Pleural biopsy, thoracoscopy

Adenosine deaminase:
Adenosine deaminase (ADA) is an enzyme of purine metabolism which
catalyses adenosine into inosine and is found in most human tissues
particularly in the lymphoid tissues.
ADA estimation has been found to be useful in the diagnosis of
tuberculosis pleural effusion and ascites.
High ADA levels have also been reported in effusions due to rheumatoid
arthritis, lymphoma, chronic lymphatic leukaemia, empyema,
parapneumonic effusions, and mesothelioma. The sensitivity and
specificity of ADA estimation in the diagnosis of EPTB is shown.
ADA exists as two isoenzymes, ADA1 and ADA2, each with unique
biochemical properties. The ADA1 isoenzyme is found in all cells with the
highest activity in lymphocytes and monocytes, whereas ADA2
isoenzyme appears to be found only in monocytes.
In tuberculosis pleural effusion, ADA2 isoenzyme is considered to be
primarily responsible for total ADA activity, while in parapneumonic
effusions, the ADA1 isoenzyme is the major isoenzyme of ADA. Thus,
measurement of individual isoenzyme of ADA can enhance the diagnostic
utility of ADA estimation in pleural effusions.

Multiseptated tuberculous empyema.


US image shows numerous linear echogenic structures in
the pleural cavity representing multiple septa, findings that are typically seen
in postprimary tuberculosis.

Abdominal tuberculosis

Abdominal tuberculosis is the term used to encompass TB of the


gastrointestinal tract, peritoneum, omentum, mesentery and its nodes
and other solid intra-abdominal organs such as liver, spleen and
pancreas.

Hepatobiliary, pancreatic and splenic tuberculosis

Hepatobiliary and pancreatic TB are rare and are often associated with
miliary tuberculosis, and occur more often in immunocompromised
patients.
The clinical manifestations are non-specific and depend on the site and
extent of disease. Anorexia, malaise, low grade fever, weight loss,
night sweats, malaena, pancreatic mass or abscess or obstructive
jaundice have all been described.
Pancreatic TB may present as acute or chronic pancreatitis or may
mimic malignancy.
Isolated splenic tuberculosis is very rare in immunocompetent
persons. Splenomegaly can occur in patients with disseminated/miliary
tuberculosis. Splenic tuberculosis presents as hypersplenism or splenic
abscess or as a solitary splenic lesion. Multiple tuberculosis abscesses
have been described in patients with HIV infection. Preoperative

Pathogenesis:
Haematogenous spread from primary
lung focus in childhood, with later
reactivation
Ingestion of bacilli in sputum
Direct spread from adjacent organs
Lymphatic spread

Diagnosis:
Imaging (CXR, plain Xray abdomen, barium enema,
sonar, CT abdomen
Colonoscopy
Laparoscopy
Ascites
Sonar findings in gastrointestinal and peritoneal
TB
Free or loculated intraabdominal fluid
Sliced bread sign
Lymphadenopathy (mixed, heterogeneous)
Bowel wall thickening
Pseudokidney sign

Neurological
tuberculosis

Neurological tuberculosis may be


classified into three clinicopathological categories:
1. tuberculosis meningitis (TBM)
(70-80%),
2. Tuberculoma (5-10%), and
3. Arachnoiditis (5-10%).

1.Tuberculosis meningitis

A majority of cases of TBM are caused by


M. tuberculosis. Isolated cases of
meningitis caused by NTM have also been
documented.
Neurological tuberculosis is invariably
secondary to tuberculosis elsewhere in the
body.
Critical event is the rupture of a
subependymally located tubercle (Rich
focus) resulting in the release of infectious
material into the subarachnoid space.

Tuberculous meningitis.
Axial contrast-enhanced T1-weighted magnetic
resonance (MR) image shows florid meningeal
enhancement that is most pronounced within the basal
cisterns.

The following features


comprise the salient
pathological features of TBM:
(i) inflammatory meningeal
exudate;
(ii) ependymitis;
(iii) vasculitis;
(iv) encephalitis; and
(v) disturbance of
cerebrospinal fluid (CSF)

Clinical features:
Highest incidence in the first three years of life
Gradual disease over 26 weeks (may be acute)
Prodromal phase: Vague illhealth, apathy, behavioral
changes, anorexia, irritability
Later headache, vomiting and fever
Focal neurological deficits and features of raised
intracranial tension may precede signs of meningeal
irritation.
Focal or generalised seizures, are encountered in 20 to 30
per cent of patients.
Cranial nerve palsies can occur in 20 to 30 per cent of
patients, the sixth nerve involvement being the most
common. Complete or partial loss of vision is a major
complication of TBM.

Various mechanisms postulated for the loss of


vision include presence of exudates around the
optic chiasma, arteritis, compression of the
anterior visual pathways due to hydrocephalus
or tuberculoma, and ethambutol toxicity among
others.
In untreated cases, progressive deterioration in
the level of consciousness, pupillary
abnormalities and pyramidal signs may
develop due to increasing hydrocephalus and
tentorial herniation.
The terminal illness is characterised by deep
coma and decerebrate or decorticate posturing.
Without treatment, death usually occurs in five
to eight weeks.

According to the severity of the illness, patients with


TBM can be categorised into three clinical stages. The
clinical staging helps to optimise therapy and to
predict the prognosis.
1) stage 1, patients are conscious and oriented with or
without signs of meningeal irritation, but no focal
neurological deficit;
2) stage 2, patients with altered sensorium or focal
deficits; and
3) stage 3, patients are comatose and have dense
deficits.
) Atypical presentations include: acute meningitic
syndrome simulating pyogenic meningitis,
progressive dementia, status epilepticus, psychosis,
stroke syndrome, locked-in-state, trigeminal
neuralgia, infantile spasm and movement disorders.

2.Intracranial tuberculomas and


single, small, enhancing brain
lesions
Tuberculoma is a mass of granulation tissue
made up of a conglomeration of microscopic
small tubercles.
The size of cerebral tuberculomas is highly
variable. In most cases their diameters
range from a few millimetres (mm) to three
to four centimeters (cm).
Intracranial tuberculomas in patients under
the age of 20 yr are usually infratentorial,
but supratentorial lesions predominate in
adults. Solitary tuberculomas are more
frequent than multiple lesions.

Patients with epilepsy who showed ring enhancing


single CT lesions have been described almost
exclusively from India. The enhancing lesion is <
2 cm, but may show considerable oedema around
it. Tuberculosis has been implicated as one of the
causes for this form of presentation.
Neurological involvement is five times more
frequent in HIV-positive compared to HIV-negative
patients. HIV infected patients account for over 50
per cent of the cases of TBM seen in the
industrialised nations. intravenous drug abusers
with AIDS exhibited increased risk of developing
neurological tuberculosis and brain abscesses.
Yechoor et al found that 20 of the 31 patients
(65%) identified as definite or probable TBM over
a 12 yr period were infected with HIV.

Diagnosis:
1. Imaging
2. Differential cell count, protein, glucose, ADA
3. TB microscopy/culture
4. (GeneXpert MTB/RIF)
5. CSF investigation:
. Lumbar puncture is hazardous if the patient has a focal
neurological deficit (cerebral space-occupying lesion) or if
fundoscopy shows papilloedema (raised intracranial
pressure). In these circumstances, a CT brain scan is helpful,
if available. Otherwise, it may be safer to start presumptive
treatment with anti-TB drugs rather than risk lumbar
puncture.
. Lumbar puncture is important for differentiating purulent
from TB meningitis. Always exclude cryptococcal meningitis
by CSF microscopy (India ink stain) and, if available, fungal
culture.

Pericardial tuberculosis
Pericardial involvement in tuberculosis may
result in
1. acute pericarditis,
2. chronic pericardial effusion,
3. cardiac tamponade or
4. pericardial constriction.
. In India, TB accounts for nearly two-thirds of the cases of
constrictive pericarditis.TB has been reported to be the cause
of acute pericarditis in four per cent of patients in the
developed world and 60 to 80 per cent of the patients in the
developing world.

. Pericardial involvemen most commonly


results from
1.

direct extension of infection from adjacent mediastinal lymph


nodes, or

TB pericarditis has the following stages:


(i) dry stage;
(ii) effusive stage;
(iii) absorptive stage; and
(iv) constrictive stage.
The disease may progress sequentially from
first to fourth stage or may present as any of
the stages.
Sometimes, pericardial TB can persent as fever
with no clinical localisation. Presence of
cardiomegaly on the chest radiograph may be
the only diagnostic clue and echocardiography
may reveal pericardial effusion.

Tuberculous pericarditis. Contrast material


enhanced CT scan demonstrates a thickened
pericardium
and bilateral pleural effusions.

Clinical features
TB pericarditis occurs most commonly in the third
to fifth decade of life.
The disease has an insidious onset and presents
with fever, malaise and weakness. The patients
may manifest pericardial rub, vague chest pain or
cardiomegaly on a chest radiograph.
Acute onset has been reported in 20 per cent of
patients and some patients can present with
cardiac tamponade.
Dyspnoea, cough, and weight loss are common
symptoms. Chest pain, orthopnoea and ankle
oedema occur in nearly 40 to 70 per cent of
patients.

Pericardial effusion:
Patients with TB pericarditis usually
present with chronic pericardial effusion.
Patients may also present acutely with
cardiac tamponade and may manifest
severe distress, retrosternal
compression, raised jugular venous
pressure (JVP) with blunt y descent,
distant heart sounds, pericardial rub and
pulsus paradoxus may be evident.

Chronic constrictive
pericarditis:
In patients with chronic constrictive pericarditis, the inflow of
blood is impeded due to thickened unyielding pericardium,
especially in the late diastole. Consequently, these patients have
systemic as well as pulmonary venous congestion
manifest exertional dyspnoea, orthopnoea, ankle oedema and
ascites. Tachycardia, raised JVP with a prominent y descent occur.
The JVP may rise further on inspiration (Kussmauls sign). Pulsus
paradoxus is seen in less than one-third of cases and signifies
presence of some fluid or a relatively elastic pericardium. A
systolic retraction of apex can be evident. A pericardial knock
may be present but murmurs are not common. The ascites is
disproportionate to the oedema (ascites praecox). Severe
elevation of venous pressure may result in congestive
splenomegaly and protein losing enteropathy resulting in
hypoalbuminaemia. After many years of hepatic venous
congestion cardiac cirrhosis may develop in some patients. The
disease worsens gradually and in chronic cases, significant
myocardial atrophy occurs due to extension of inflammation and

Diagnosis:
The diagnosis usually rests on
1. suggestive constitutional and
2. cardiovascular features and
3. investigation findings (ECG, CXR and
echocardiography).
. It is important to exclude uraemia
and Kaposi sarcoma.

Cardiovascular symptoms and


signs:
Cardiovascular symptoms
chest pain
shortness of breath
cough
dizziness and weakness (low cardiac output)
leg swelling
right hypochondrial pain (liver congestion)
abdominal swelling (ascites)
Always test a patient with signs of a pleural effusion for a succussion splash.

Cardiovascular signs
tachycardia
low blood pressure
pulsus paradoxus
raised jugular venous pressure (JVP) with small amplitude "a" and "v"
waves
impalpable apex beat
quiet heart sounds
pericardial friction rub
signs of right-sided heart failure (e.g. hepatomegaly, ascites, oedema)

CXR
large globular heart
clear lung fields
pleural fluid
ECG
tachycardia
ST and T wave changes
low voltage QRS complexes
sometimes electrical
alternans (alternating positive
and negative R
waves, reflecting a heart that
moves with each beat within
the pericardial fluid)
Echocardiography
pericardial fluid
strands crossing between
visceral and parietal
pericardium

Pitfalls in diagnosis of
pericardial effusion
Clinicians have misdiagnosed
pericardial effusion as the following:
congestive cardiac failure;
hepatoma or amoebic liver abscess
(enlarged liver);
bilateral pleural effusions.
Pericardiocentesis
This is only safe under the following
conditions:
a) echocardiography has confirmed a
moderate to large pericardial
effusion;
b) the operator is experienced.
The signs may be subtle. Assess
carefully any patient with oedema
or ascites with the possibility of
pericardial effusion in mind.
Therapeutic pericardiocentesis is
necessary if there is cardiac
tamponade (acute life-threatening
cardiac impairment).

Differential diagnosis:

Apart from TB, the differential


diagnosis of pericardial effusion
includes the following:
Transudates: uraemia, heart
failure, liver failure,
hypothyroidism;
Exudates: malignancy, bacterial
pericardial empyema,
inflammatory diseases.

In populations with high TB/HIV


prevalence,TB the most likely
treatable cause of pericardial
effusion. It may be safer for the
patient to start presumptive anti-TB
treatment than to undergo diagnostic
pericardiocentesis.

Bone and joint


tuberculosis
Skeletal tuberculosis is a haematogenous

infection and affects almost all bones.


Tuberculosis commonly affects the spine and
hip joint. Other sites of involvement include
knee joint, foot bones, elbow joint and hand
bones. Rarely, it also affects shoulder joint.
Two basic types of disease patterns seen:
1. granular and
2. exudative (caseous).
. Though both the patterns have been observed
in osseous and synovial tuberculosis infection,
one form may predominate.

Spinal tuberculosis (TB spine) is the most


common form of skeletal tuberculosis.
Majority of patients are under thirty years
of age at the time of diagnosis.
Constitutional symptoms such as
weakness, loss of appetite and weight,
evening rise of temperature and night
sweats generally occur before the
symptoms related to the spine manifest.
Lower thoracic and lumbar vertebrae are
the most common sites of spinal
tuberculosis followed by middle thoracic
and cervical vertebrae.

Usually, two contiguous vertebrae are involved but several


verebrae may be affected and skip lesions are also seen.
The infection begins in the cancellous area of vertebral body
commonly in epiphyseal location and less commonly in the
central or anterior area of vertebral body .
1. The infection spreads and destroys the epiphyseal cortex,
the intervertebral disc and the adjacent vertebrae.
2. It may spread beneath the anterior longitudinal ligament
to reach neighbouring vertebrae.
3. The exudate penetrates the ligaments and follows the path
of least resistance along fascial planes, blood vessels and
nerves, to distant sites from the original bony lesion as cold
abscess.
. The vertebral body becomes soft and gets easily
compressed to produce either wedging or total collapse.
Anterior wedging is commonly seen in the thoracic spine
where the normal kyphotic curve accentuates the pressure
on the anterior part of vertebrae.

In the cervical region,


1. the exudate collects behind prevertebral
fascia and may protrude forward as a
retropharyngeal abscess.
2. The abscess may track down to the
mediastinum to enter into the trachea,
oesophagus or the pleural cavity.
3. It may spread laterally into the
sternomastoid muscle and form an
abscess in the neck.
. Retropharyngeal abscess can present with
local pressure effects such as dysphagia,
dyspnoea, or hoarseness of voice.

In the thoracic spine,


1. the exudate may remain confined locally for
a long time and may appear in the
radiographs as a fusiform or bulbous
paravertebral abscess and may compress the
spinal cord.
2. Rarely, a thoracic cold abscess may follow
the intercostal nerve to appear anywhere
along the course of nerve.
3. It can also penetrate the anterior longitudinal
ligament to form a mediastinal abscess or
4. pass downwards through medial arcuate
ligament to form a lumbar abscess.

The exudate formed at lumbar


vertebrae
1. most commonly enters the psoas sheath to manifest
radiologically as a psoas abscess or clinically as a
palpable abscess in the iliac fossa.
2. Abscess can gravitate beneath the inguinal ligament
to appear on the medial aspect of thigh. It can spread
laterally beneath the iliac fascia to emerge at the iliac
crest near anterior superior iliac spine. Sometimes an
abscess forms above the iliac crest posteriorly.
3. Collection can follow the vessels to form an abscess in
Scarpas triangle or gluteal region if it follows femoral
or gluteal vessels respectively.
.
Flexion deformity of hip develops due to psoas
abscess.

Paraplegia (Potts paraplegia) is the most


serious complication of spinal tuberculosis
and its occurrence is reported to be as high as
30 per cent in patients with spinal
tuberculosis. Early onset paraplegia develops
during the active phase of infection.
Paraplegia of late onset can appear many
years after the disease has become quiescent
even without any evidence of reactivation.
Most commonly paraplegia develops due to,
1. mechanical pressure on the cord,
2. but in a small number of patients cord
dysfunction may occur due to nonmechanical
causes.

Clinical presentation of tuberculosis of


the hip and knee joints depends on the
clinicopathological stage and each
stage has a definite pattern of clinical
deformity. Pain, circumferential
reduction of movements at the joint
are evident. Night cries may develop
due to relaxation of muscle spasm and
unguarded movements at the joint .
Tuberculosis osteomyelitis may mimic
chronic osteomyelitis of other causes.

Genitourinary
tuberculosis
Genitourinary tuberculosis
(GUTB) complicates three to four per cent

of patients with pulmonary tuberculosis.


Haematogenous dissemination from an active site of infection results
in GUTB. Initially metastatic lesions (tubercles) are formed in the
kidneys. Macroscopic progression of the disease is often unilateral.
1. Usually, these lesions heal spontaneously or as a result of treatment.
2. However, they may enlarge even after years of inactivity and rupture
into the nephrons producing bacilluria. There is descending spread of
infection, inflammation and scarring.
. Active GUTB usually develops 5 to 25 yr after the primary pulmonary
infection and is usually encountered between the second and fourth
decades of life.
. Patients present with: dysuria, haematuria which may be
painless, flank pain, renal mass, sterile pyuria, and recurrent urinary
tract infection. Rarely, acute presentation mimicking pyelonephritis
has also been described. Other uncommon presentations include: non
healing wounds, sinuses or fistulae, haemospermia among others.

Female genital tuberculosis


1. Primary female genital tuberculosis has rarely been
described in female partners of males affected by
active GUTB.
2. More often, female genital tuberculosis is secondary
to tuberculosis infection elsewhere in the body.
. Haematogenous or lymphatic spread is the most
common method of spread. Infection may also
spread from the contiguous intraabdominal sites
through the fallopian tubes.
. Female genital tuberculosis is an important cause of
infertility. Patients may also present with chronic
lower abdominal or pelvic pain, or alterations in the
menstrual pattern.

Cutaneous tuberculosis

Cutaneous tuberculosis accounts for 0.11 to 2.5


per cent of all patients with skin diseases.
Several clinical types of cutaneous tuberculosis.
1. In those not previously exposed to M.
tuberculosis, miliary tuberculosis of the skin and
tuberculosis chancre have been described.
2. Previously sensitised hosts develop, lupus
vulgaris, scrofuloderma, tuberculosis verrucosa
cutis. Other lesions seen are tuberculids which
include lichen scrofulosorum; papulonecrotic
tuberculid; erythema induratum; and erythema
nodosum.

Lupus vulgaris is the most common variety seen in


India followed by tuberculosis verrucosa cutis and
scrofuloderma. The other types are distinctly rare.
Localised and generalised skin complications due
to Bacille Calmette-Guerin (BCG) vaccination have
also been described.
In patients with HIV infection and AIDS, the lesions
may not fit into the above described categories
and usually present as papules, nodules, vesicles
or induration. Ulceration and discharge from the
surface of the lesions may occur.
The diagnosis is usually not suspected clinically
and it has been suggested that all atypical
cutaneous lesions developing in
immunosuppressed individuals should be biopsied
and subjected to mycobacterial culture

Tuberculosis in otorhinolaryngology

Otorhinolaryngological TB
constitutes less than five per
cent of all cases of EPTB.
Focus has shifted on to
otorhinolaryngological TB
with the advent of HIV
infection and AIDS.

Tuberculosis of larynx
In the present era, in countries where TB is highly endemic,
almost all patients with laryngeal tuberculosis have been found to
have radiological evidence of pulmonary TB and many of them
may be sputum smear-positive. On the contrary, in countries with
a low prevalence of tuberculosis, associated pulmonary
tuberculosis is rarely seen in patients with laryngeal TB.
Clinical features: Patients often present with hoarseness of voice.
Pain is also an important feature which may radiate to one or
both ears and may lead to odynophagia.
D/D:
1. Occasionally, patients may present with rapid onset of
hoarseness of voice similar to that encountered in acute viral
laryngitis.
2. Laryngeal tuberculosis may co-exist with carcinoma. Clinical
features of these conditions may overlap and the lesions may
look similar.

Tuberculosis of the pharynx oral cavity and salivary glands


Tuberculosis involvement of the tonsils and pharynx is uncommon.
The presenting features include:
(i) ulcer on the tonsil or oropharyngeal wall;
(ii) granuloma of the nasopharynx; and
(iii) neck abcess.
The oral cavity is an uncommon site of involvement by tuberculosis.
Infection in the oral cavity is usually acquired through infected sputum
coughed out by a patient with open pulmonary tuberculosis or by
haematogenous spread.
Tongue is the most common site of involvement and accounts for
nearly half the cases. The lesions are usually found over the tip,
borders, dorsum and base of the tongue.
They may be single or multiple, the lesions may or may not be painful.
Other sites of involvement include floor of mouth, soft palate, anterior
pillars and uvula. Secondary involvement of the draining lymph nodes
may occur. Majority of these patients also have pulmonary
tuberculosis.

TB sialitis
TB sialitis is usually secondary to tuberculosis infection of
the oral cavity or primary pulmonary tuberculosis.
Primary infection of the salivary glands is also known,
but, is rare.
Parotid gland is most commonly involved.
Clinical presentation can be acute or chronic. Acute
presentation may resemble acute non-tuberculosis sialitis
and clinical differentiation may be difficult. Occasionally,
the diagnosis of tuberculosis may be a surprise following
surgery performed for a suspected salivary gland tumour.
Unsuspected tuberculosis parotid abscess may be
wrongly drained mistaking it to be a pyogenic abscess.
This may lead to the formation of a persistent sinus.

Tuberculosis of the ear


Tuberculosis of the external ear is uncommon.
However, lupus vulgaris of the external ear has been
reported.
Tuberculosis of the ear develops when the bacilli invade
the eustachian tube while the infant is being fed, or, by
haematogenous spread to the mastoid process.
The focus in the middle ear cleft may present as
painless otorrhoea. Pale granulation tissue may be
present in the middle ear with dilatation of vessels in
the anterior part of the tympanic membrane. Multiple
perforations of tympanic membrane may occur as a
result of caseation necrosis. Facial nerve palsy may
sometimes develop.

Tuberculosis of paranasal sinuses and nasopharynx

Tuberculosis of nose, paranasal sinuses and


nasopharynx is uncommon. However occasionally
maxillary sinus may be involved.
Other sites which can be involved include
inferioturbinate, septal mucosa and the vestibular
skin.
Nasal discharge, mild pain and partial nasal
obstruction are important presenting features.
Involvement of nasolacrimal duct can rarely occur.
Tuberculosis of the nose can cause complications
like septal perforation, atrophic rhinitis and scarring
of nasal vestibule.

Ocular tuberculosis
Ocular involvement has described in 2 to 30 per cent of patients
with tuberculosis, and usually develops as a result of
haematogenous dissemination.
While tuberculosis can affect all the part of the eye, choroid is the
most commonly affected structure. Primary ocular tuberculosis
though has been described is extremely rare. Tuberculosis affects
the eyelids infrequently. Lupus vulgaris may spread to the face and
involve the eyelid.
Conjunctival tuberculosis and lupus vulgaris are the common
manifestations of primary tuberculosis while tuberculids and
phlyctenulosis occur in postprimary tuberculosis. Phlyctenulosis can
involve conjunctiva, cornea or lid margin.
CHOROIDAL TUBERCLES, when present, can provide valuable
diagnostic clues to life threatening forms of disseminated
tuberculosis such as miliary tuberculosis. These may be single or
multiple and vary in size from quarter of a disc diameter to several
disc diameters and are most frequently situated at the posterior
pole.

Tuberculosis of the breast

1.

2.
.

Tuberculosis mastitis can occur as primary disease or can


be secondary to tuberculosis elsewhere in the body.
Primary tuberculosis mastitis is extremely rare and is
thought to occur due to direct inoculation of the breast by
M. tuberculosis through skin abrasions or duct openings in
the nipple.
Secondary involvement of breast is more common.
The organisms may reach the breast through lymphatic
route or haematogenous routes, or by contiguous spread
from the ribs, pleural space.. Lymphatic spread by
retrograde extension from the axillary lymph nodes is
considered to be the most common mode of spread though
spread from cervical and mediastinal lymph nodes has been
occasionally reported.
Clinical presentation is atypical and often, histopathological
evidence suggests the diagnosis.

Disseminated/miliary
tuberculosis
Disseminated tuberculosis (DTB) refers to involvement of two
or more non-contiguous sites.
Results from either a recent primary infection or the erosion of
a tuberculous lesion into a blood vessel.
During primary infection,
small numbers of tubercle bacilli gain access to the circulation
through the lymphatics and disseminate to visceral sites
which have rich vascular supply and good oxygenation such
as the liver, spleen, bone marrow and the brain.
foci heal by calcification in a majority of the patients.
In the post-primary period,
acute miliary tuberculosis (MTB) can occur when these foci fail
to heal and progress. Later in life, reactivation of these latent
foci, caseation and erosion into blood vessels can result in
haematogenous embolisation and the development of MTB.

MTB and ARDS:


Though the association of MTB and acute lung
injury (ALI) and acute respiratory distress sydnrome
(ARDS) is well known, only a few cases of this
association have been published.
Severe pulmonary vascular damage has been
implicated to be the pathophysiological basis for
the development of ARDS in patients with MTB.
Increases in CD4+ T- lymphocytes induced by
HAART with subsequent inflammation in tissues
affected by ongoing infection have been postulated
to be the mechanism responsible for ARDS
(immune reconstitution phenomenon).
In patients with MTB complicated by ARDS, the
classical miliary mottling occurs less commonly and

Clinical presentation:
Even in areas where TB is highly endemic, the diagnosis of MTB can be
difficult as the clinical symptoms have been subacute and non specific
and the chest symptoms can be obscure till late in the disease. Patients
present with constitutional features rather than respiratory symptoms.
Skin involvement in the form of erythematous macules and papules and
unusual manifestations such as ulcerative lesions have also been
described.
Neurological involvement in the form of meningitis or tuberculomas is
common.
Overt adrenal insufficiency at presentation, or during treatment has also
been described.
Patients present with constitutional features rather than respiratory
symptoms.They may have hepatosplenomegaly and choroidal tubercles
(fundoscopy).
Often the presentation is associated with fever of unknown origin and
wasting may be marked. Miliary TB is an underdiagnosed cause of endstage wasting in HIV-positive individuals.A high index of suspicion is
necessary.

Diagnosis:
CXR shows diffuse, uniformly distributed, small
miliary shadows. "Miliary" means "like small
millet seeds".The CXR can appear normal in
advanced cases because of severe
immunosuppression and therefore inability to
mount an inflammatory response.
Full blood count may show pancytopenia. Liver
function tests may be abnormal.
Bacteriological confirmation (smears or
mycobacterial culture) is sometimes possible
from sputum, cerebrospinal fluid, bone
marrow, liver or blood.

Differential Diagnosis:
The differential diagnosis includes the
following:
1. The syndrome of HIV wasting disease
(sometimes referred to as slim disease),
2. Bacteraemia (including typhoid fever),
3. disseminated carcinoma,
4. disseminated infection with "atypical"
mycobacteria, trypanosomiasis (in endemic
regions) and
5. connective tissue diseases.

Complications and sequele of EPTB:

Diagnosis
Part

Methodological issues
Definitive diagnosis of tuberculosis involves demonstration of
M. tuberculosis by microbiological, cytopathological or
histopathological methods.
Clinical presentation of EPTB is atypical. Especially when the
disease involves obscure occult sites, EPTB may not even be
considered in the initial list of differential diagnosis.
Further, invasive methods may have to be employed to
secure tissue/body fluids for analysis. Many times
representative tissue/body fluid may not be accessible.
Even when adequate tissue is procured, the pathological
findings may be suggestive of granulomatous infection
which encompasses a wide range of differential diagnoses
rather than definitive tuberculosis.
Therefore, the clinicians more often rely upon the clinical
impression, radiological and endoscopic appearances and
nonconventional diagnostic methods as evidence to diagnose
EPTB.

Principles of diagnosis
When EPTB is suspected as a possible diagnosis, every
attempt should be made to procure tissue/relevant body
fluid for diagnostic testing.
Most accessible tissue should be procured for
histopathological, cytopathological and micrbiological
diagnosis.
For example, when working up a patient with suspected
lymph node tuberculosis, the most easily accessible
representative peripheral lymph node should be excised
and subjected to diagnostic testing. Similarly,
cerebrospinal fluid (CSF) and ascitic fluid examination
provide most valuable diagnostic clue in patients with
neurological and peritoneal tuberculosis respectively.

With the advent of ultrasound scan and


subsequently CT scan and the magnetic
resonance imaging (MRI) and widespread
availability of upper gastrointestinal endoscopy,
colonoscopy, laparoscopy, cystoscopy and
biopsy under visual guidance and other invasive
investigations such as hysterosalpingography
and colposcopy, tremendous progress has been
achieved in precise anatomical localisation of
the lesions of EPTB antemortem.
If no accessible tissue/fluid is available for
analysis, radiologically guided fine needle
aspiration and cytopathology (FNAC) or biopsy
may be required to secure tissue for diagnosis.

Tuberculin Skin Test:


Tuberculin skin test: In countries like
India where tuberculosis is highly
endemic, tuberculin skin test result
alone is not sufficient evidence to
diagnose EPTB in adult patients.

PPD Purified Protein


Derivatives:
The tuberculin test is based on the fact that infection with M.
tuberculosis produces a delayed-type hypersensitivity reaction
to certain antigenic components of the organism that are
contained in extracts of culture filtrates called tuberculins.
Most of the constituents of PPD are small proteins with
molecular masses of approximately 10,000 Da, but there are
also polysaccharides and some lipids present. The relatively
small size of the protein constituents in PPD is the reason that
PPD does not sensitize individuals who have not been exposed
to mycobacteria.
Tuberculins and PPDs have been prepared from other
mycobacterial species, but these materials are less sensitive
and specific for diagnosis of nontuberculous mycobacterial
infections than is PPD for M. tuberculosis infections

Dose of PPD:
The standard 5-tuberculin unit (TU) dose
of PPD-S is defined as the delayed skin
test activity contained in a PPD-S dose of
0.1 mg/0.1 ml.
The standard test dose of a commercial
PPD preparation is defined as the dose of
the product that is biologically equivalent
to that contained in 5 TU of PPD-S (i.e., it
elicits reactions of equivalent size +/_
20%).

Precaution while
handling:
PPD, when diluted in a buffered diluent, is adsorbed in
varying amounts by glass and plastics. A small amount of the
detergent Tween 80 is added by the manufacturer to the
diluent for PPD to reduce adsorption.
To minimize reduction in potency by adsorption, tuberculin
should never be transferred from one container to another,
and skin tests should be given as soon after the syringe has
been filled as possible.
Following these procedures will also help avoid
contamination: test doses should always be removed from
the vial under strictly aseptic conditions, and the remaining
solution should be kept refrigerated (not frozen).
Tuberculin should be stored in the dark as much as possible
and exposure to strong light should be avoided.

Administration of Test:
The test is administered by injecting 0.1 ml of 5-TU PPD
intradermally (Mantoux method) into the volar or dorsal surface of
the forearm. Other areas may be used, but the forearm is preferred.
The use of a skin area free of lesions and away from veins is
recommended.
The injection is made using a one quarter- to one-half-inch, 27gauge needle and a tuberculin syringe.
The tuberculin should be injected just beneath the surface of the
skin, with the needle bevel upward or downward . A discrete, pale
elevation of the skin (a wheal) 6 to 10 mm in diameter should be
produced when the injection is done correctly.
If it is recognized that the first test was improperly administered,
another test dose can be given at once, selecting a site several
centimeters away from the original injection. A note in the record
should indicate the site chosen for the second test.

Reading of Test:
Tests should be read between 48 and 72 h after injection,
when the induration is maximum. Tests read after 72 h
tend to underestimate the true size of induration.
Reading should be performed in a good light, with the
forearm slightly flexed at the elbow.
The basis of reading is the presence or absence of
induration, which may be determined by inspection (from
a side view against the light as well as by direct light)
and by palpation.
For standardization, the diameter of induration should be
measured transversely to the long axis of the forearm
and recorded in millimeter. The absence of induration
should be recorded as 0 mm, not negative.

Immunologic Basis for the Tuberculin Reaction:


The reaction to intracutaneously injected tuberculin is the classic example of a
delayed (cellular) hypersensitivity reaction. T cells sensitized by prior infection are
recruited to the skin site where they release lymphokines (127). These lymphokines
induce induration through local vasodilatation, edema, fibrin deposition, and
recruitment of other inflammatory cells to the area.
Features of the reaction include
(1) its delayed course, reaching a peak more than 24 h after injection of the antigen;
(2) its indurated character; and
(3) its occasional vesiculation and necrosis.
Reactivity of the PPD provides a general measure of a persons cellular immune
responsiveness .
Typically, the reaction to tuberculin begins 5 to 6 h after injection, causes maximal
induration at 48 to 72 h, and subsides over a period of days.
In a few individuals (the elderly and those who are being tested for the first time), the
reaction may not peak until after 72 h . Such delayed reactions do not alter the
intrepretation of the test.
Immediate hypersensitivity reactions to tuberculin or constituents of the diluent can
also occur. These reactions disappear by 24 h, and should not be confused with
delayed hypersensitivity reactions. However, if the immediate reaction is severe, it
may be prudent not to retest. Symptom screening is suggested if these individuals are
part of a regular tuberculin skin testing program (e.g., healthcare workers).

IGRA:
Interferon-y (IFN-y) is a cytokine
produced by activated T-lymphocytes.
It plays a fundamental role in the
immune response to tuberculosis.
High levels of IFN-y have been
reported in tuberculosis pleural
effusions, possibly related to in situ
stimulation of CD4+ T lymphocytes by
tuberculosis antigens.

In 2005, CDC published guidelines for using the QuantiFERON-TB


Gold test (QFT-G) (Cellestis Limited, Carnegie, Victoria, Australia)
Subsequently, two new interferon gamma (IFN- ) release assays
(IGRAs) were approved by (FDA) as aids in diagnosing M.
tuberculosis infection, both latent infection and infection
manifesting as active tuberculosis. These tests are the
QuantiFERON-TB Gold In-Tube test (QFT-GIT) (Cellestis Limited,
Carnegie, Victoria, Australia) and the T-SPOT.TB test (T-Spot)
(Oxford Immunotec Limited, Abingdon, United Kingdom).
Although data on the accuracy of IGRAs and their ability to
predict subsequent active tuberculosis are limited, to date, no
major deficiencies have been reported in studies involving
various populations.
FDA-approved IGRAs in the diagnosis of M. tuberculosis infection
in adults and children. In brief, TSTs and IGRAs (QFT-G, QFT-GIT,
and T-Spot) may be used as aids in diagnosing M. tuberculosis
infection. They may be used for surveillance purposes and to
identify persons likely to benefit from treatment.

General Recommendations for


Use Of IGRA and TST:

1. Situations in Which a TSTIs


Preferred But an IGRA Is
Acceptable:
. A TST is preferred for testing children
aged <5 years. Use of an IGRA in
conjunction with TST has been
advocated by some experts to increase
diagnostic sensitivity in this age group.

2. Situations in Which Either a


TST or an IGRA May Be Used
Without Preference:

1.
2.
3.
.
.

An IGRA or a TST may be used without preference to test recent


contacts of persons know or suspected to have active
tuberculosis.
Advantage:
IGRAs offer the possibility of detecting M. tuberculosis infection
with greater specificity than with a TST.
Also, unlike TSTs, IGRAs do not boost subsequent test results and
can be completed following a single patient visit.
Disadvantage:
ability of IGRAs to predict subsequent active tuberculosis are
limited. If IGRAs are to be used in contact investigations, negative
results obtained prior to 8 weeks after the end of exposure
typically should be confirmed by repeat testing 810 weeks after
the end of exposure. This recommendation is similar to one used
for TST, because data on the timing of IGRA conversion after a
new infection are not currently available. Use of the same test
format for repeat testing will minimize the number of conversions
that occur as a result of test differences.

An IGRA or a TST may be used


without preference for :
periodic screening of persons who might have occupational exposure to M.
tuberculosis (e.g., surveillance programs for health-care workers) with special
considerations regarding conversions and reversions. For serial and periodic
screening, IGRAs offer technical, logistic, and possible economic advantages
compared with TSTs but also have potential disadvantages.
Advantages include the ability to get results following a single visit. Two-step testing
is not required for IGRAs, because IGRA testing does not boost subsequent test
results.
Disadvantages of IGRAs in this setting include a greater risk of test conversion due to
false-positive IGRA results with follow-up testing of low-risk health-care workers who
have tested negative at prior screening.

CDC has published criteria for identifying conversions


for TSTs and IGRAs.
TST conversion is defined as a change from negative to positive with an increase of
10 mm in induration within 2 years. TST conversion is associated with an increased
risk for active tuberculosis.
An IGRA conversion is defined as a change from negative to positive within 2 years
without any consideration of the magnitude of the change in TB Response.
Using this lenient criterion to define IGRA conversion might produce more
conversions than are observed with the more stringent criteria applied to TSTs.
Furthermore, an association between an IGRA conversion and subsequent disease
risk has not been demonstrated. The criteria for interpreting changes in an IGRA that
identify new infections remain uncertain.

3. Situations in Which an IGRA


Is Preferred But a TSTIs
Acceptable:

An IGRA is preferred for testing persons from groups


that
1. historically have low rates of returning to have TSTs
read. For example, use of an IGRA might increase test
completion rates for homeless persons and drug-users.
The use of IGRAs for such persons can increase test
completion rates, so control efforts can focus on those
most likely to benefit from further evaluation and
treatment.
2. An IGRA is preferred for testing persons who have
received BCG (as a vaccine or for cancer therapy). Use
of IGRAs in this population is expected to increase
diagnostic specificity and improve acceptance of
treatment for LTBI.

4. IGRA and a TSTMay Be


Considered:

Although routine testing with both a TST and an IGRA is not


generally recommended, results from both tests might be
useful when the initial test (TST or IGRA) is negative in the
following situations:
1) when the risk for infection, the risk for progression, and the
risk for a poor outcome are increased (e.g., when persons with
HIV infection or children aged <5 years are at increased risk for
M. tuberculosis infection) or
2) when clinical suspicion exists for active tuberculosis (such as
in persons with symptoms, signs, and/or radiographic evidence
suggestive of active tuberculosis) and confirmation of M.
tuberculosis infection is desired.
In such patients with an initial test that is negative, taking a
positive result from a second test as evidence of infection
increases detection sensitivity. However, multiple negative
results from any combination of these tests cannot exclude M.
tuberculosis infection.

Histopathological, cytopathological and


microbiologial examination of tissue
specimens and body fluids

Fine needle aspiration cytopathology (FNAC),


biopsy:
In patients with lymph node tuberculosis,
excision biopsy of the most accessible peripheral lymph node
confirms the diagnosis most of the times.
CT scan is helpful in localising intrathoracic and intraabdominal
lymphadenopathy and radiologically guided FNAC and biopsy.
When available, video-assisted thoracoscopic surgery (VATS)
can be a valuable minimally invasive procedure to procure
tissue for diagnostic testing in patients with intrathoracic
lymphadenopathy and pleural disease.
Laparoscopy will facilitate visual inspection of the lesions and
faciliatate procurement of tissue for histopathological
confirmation of the diagnosis.
Transporting the collected lymph node specimen in Kirschners
transport medium is helpful in increasing the microbiological
yield.

Examination of body fluids and other


biochemical
Tests
Pleural fluid:
The pleural fluid is typically clear or straw coloured,
but cloudy or serosanguinous fluid may also be
obtained. The pleural fluid is exudative and
lymphocyte rich. Early in the disease, the pleural
fluid may reveal predominantly neutrophils, but on
serial thoracocenteses, lymphocytosis may become
evident. Presence of a large number of mesothelial
cells (> 1% of white blood cells) is a strong evidence
against the diagnosis of tuberculosis, though, a few
cases with numerous mesothelial cells in the fluid
have been reported .

Cerebrospinal fluid:
Clear CSF with moderately raised cells and protein and
low glucose constitute the typical CSF picture of TBM.
However, these characteristics are shared by other forms
of chronic meningitis and partially treated pyogenic
meningitis.
In the presence of coexisting spinal meningitis and spinal
block the CSF may be xanthochromic.
If allowed to stand, a pellicle or cobweb may form,
indicating the presence of fibrinogen. The pellicle is
highly suggestive but not pathognomonic of TBM.
CSF protein has been reported to be normal in some
patients with AIDS and TBM.
CSF glucose levels are abnormal in the majority of cases,
being less than 40 per cent of the corresponding blood
sugar level. However, CSF glucose levels are never
undetectable as in patients with pyogenic meningitis.

Pericardial fluid:
Echocardiography, pericardiocentesis and examination
of pericardial fluid can help in confirming the
diagnosis of pericardial tuberculosis.

Urine:
The yield of urine examination by smear and culture
for detecting the tubercle bacillus is low probably
because of the intermittent shedding of the bacilli.
Nevertheless, in patients with suspected genitourinary
tuberculosis, urine examination is mandatory.

Cold abscess pus:


Smear and culture examination of the pus aspirated
from cold abscesses either directly or under
radiological guidance can be rewarding and must be
attempted whenever feasible.

Imaging:
Plain radiograph:
The association of pulmonary tuberculosis assessed by the chest
radiograph in patients with various forms of EPTB is depicted.
In patients with pleural tuberculosis,
the chest radiograph usually reveals a unilateral pleural effusion.
Sometimes the pleural effusion or empyema can be encysted or
multiloculated.
Encysted effusion may be confused with a mass lesion of the
pleura, mediastinum, chest wall and lungs. Most often encystment
occurs in the costoparietal regions, usually along the posterior
parietal pleural surface on the right side.
A lateral decubitus film may be useful in dstinguishing
subpulmonic encystment from subpulmonic of free fluid as both
these conditions present with a raised hemidiaphragm with
convexity lateral than usual with or without a blunted
costophrenic angle. Very rarely, encysted mediastinal pleural
effusion can present as an unexplained bulge of the mediastinum.

The hallmark of acute disseminated MTB


is the miliary pattern on the chest
radiograph. The term miliary refers to the
millet seed size of the nodules (2-3
mm) seen on classical chest films.
Some patients with MTB, however, may
have normal chest radiographs and some
may have patterns that are
indistinguishable from interstitial
pneumonia. Some of the patients may
manifest coalescent opacities. When
patients with MTB develop ARDS, the
chest radiograph may be identical to that
seen in ARDS due to other causes.

Intravenous pyelography and


percutaneous nephrogram: are useful in imaging
GUTB.

Ultrasonography: Ultrasonography of the chest may


be helpful in demonstrating winding structures of different
lengths which may represent fibrin bands, mobile delicate
septations, regular pleural thickening, and occasional
nodularity amidst the effusion. Ultrasonography and CT scan
are useful in the diagnosis of encysted and multiloculated
pleural effusions.

Computerised tomography and magnetic


resonance Imaging: In patients with pleural effusion
and empyema, contrast enhanced (CE) CT scan of the thorax
may be useful in identifying the underlying pulmonary lesion,
mediastinal, hilar or paratracheal lymphadenopathy and
assessing the pleural loculation and thickening. Sometimes,
CECT of the thorax has also been used to assess pericardial
thickening in patient with pericardial effusion.

Abdominal CT scan scores over ultrasonography for


detecting high density ascites.
Retroperitoneal, peripancreatic, porta hepatis and
mesenteric/omental lymph node enlargement may
be evident. Abdominal CT scan also detects caseous
necrosis of lymph node which appears as low
attenuating, necrotic centres and thick, enhancing
inflammatory rim.
Granulomas or abscesses in the liver, pancreas and
spleen may be seen.
In addition to ascites, mesenteric infiltration, omental
masses, peritoneal enhancement/thickening and
disorganised masses of soft tissue densities may be
seen.
In patients with DTB/MTB, CT scan and MRI scan may
reveal evidence of neurotuberculosis, intraabdominal
lymphadenopathy, infiltrative lesions in liver, spleen

CT scan or MRI of the brain:


may reveal thickening and enhancement of basal meninges, hydrocephalus,
infarction, periventricular oedema, and mass lesions due to associated
tuberculoma or tuberculosis abscess. Common sites of exudates are basal
cisterna ambiens, suprasellar cistern and sylvian fissures. Serial CT scans are
very helpful in assessing the course of tuberculomas and hydrocephalus.

Gadolinium enhanced MRI

is superior to the CT scan in detection


of basal meningeal enhancement and smal tuberculomas. Contrast enhanced
MRI has been found to be superior to the contrast enhanced CT scan in
detection of diffuse and focal meningeal granulomatous lesions, in delineating
focal infarcts of the basal ganglia and diencephalon. Further, MRI is superior to
CT in defining the presence, location and extent of associated brainstem
lesions.

MRI of the spine

is also useful in the diagnosis of lesions of spinal

tuberculosis.
If there is a high index of suspicion of the diagnosis of MTB and the chest
radiograph is atypical, it is suggested that high resolution computed
tomographic scan (HRCT scan) be done to support the diagnosis. HRCT
scan is superior to the conventional CT scan in defining the parenchymal detail.
Further, HRCT of the chest with contrast can also be useful in detecting lymph
nodal enlargement, calcification and pleural lesions.

Echocardiography and cardiac


catherisation :

Echocardiography is useful for detecting the presence of


pericardial fluid and features such as collapse of right atrial
or right ventricular free wall in diastole which are diagnostic
of cardiac tamponade. In fact, these features may
sometimes precede the other clinical evidence of
pericardial tuberculosis.
Echocardiogram, however, is not an accurate test to detect
pericardial thickening.
Indirect echocardiographic signs such as flat posterior left
ventricular wall motion in the diastole, premature opening
of the pulmonary valve, may suggest chronic constrictive
pericarditis.
In cardiac tamponade,

reveals

cardiac catheterisation

a prominent Y descent in the right atrial


tracing. In chronic constrictive pericarditis, a prominent Y
descent in the atrial pressure tracing and a dip-plateau

Serologial, molecular and other non-conventional methods:

A number of non-conventional diagnostic methods are often


resorted to for diagnosing EPTB. These test results are relied upon
as concrete evidence to initiate or withold antituberculosis
treatment.
When many of these non-conventional methods are validated at the
time of initial introduction, the criteria employed to define the gold
standard for diagnosis against which these methods are
standardised would include a clinical presentation compatible with
tuberculosis and good response to antituberculosis treatment.
Subsequently, the same diagnostic tests are recommended for
substantiating the clinical diagnosis. Further, the small sample size
and the lack of reproducibility of the tests in most studies render
the information generated by these tests inconclusive.
It should be remembered that a positive non-conventional test may
perhaps rule in a diagnsosis, but certainly a negative test cannot
rule out a diagnosis of tuberculosis Thus, it is not suprising that
the diagnosis of EPTB is often delayed or missed.

Immunodiagnostic
methods
Applied
to
body
fluids:
Most often, enzyme linked immunosorbent
assay (ELISA) for detecting mycobacterial

antigens, antibodies and immunecomplexes in the


blood and body fluids have been used in the
diagnosis of EPTB.
Some workers have advocated testing for a panel of
antigens rather than single antigens.
However, ELISA based methods for the detection of
mycobacterial antigens in body fluids have been
resorted to most often for the diagnosis of
neurological (CSF) and pleural tuberculosis (pleural
fluid).

Applied to blood:

The diagnostic utility of serodiagnostic methods applied to the


blood samples in patients with EPTB is controversial.
The overall positivity rate for the test was 75 per cent . The
positivity rate of the test in serum and/or CSF was 79.2 per cent
in neurotuberculosis and 62.5 per cent for other forms of EPTB.
In another study, the utility of detecting immunoglobulin G (IgG)
and immunoglobulin A (IgA) against antigen was studied in 42
patients with confirmed EPTB, none had clinical or radiological
evidence of pulmonary involvement. In addition, 24 subjects with
healed pulmonary or EPTB, 44 patients with a defined disease
other than tuberculosis, and 88 healthy volunteers were studied.
In patients with EPTB, the sensitivity and specificity of IgG and
IgA tests were 0.738 and 0.961; and 0.69 and 0.936 respectively.
When both the results were combined, the sensitivity was 0.809
and the specificity was 0.923245 .
Detection of lipopolysaccharide antigen (LPS) has also been
found to be useful in the diagnosis of EPTB.

Adenosine deaminase:

Adenosine deaminase (ADA) is an enzyme of purine


metabolism which catalyses adenosine into inosine and is
found in most human tissues particularly in the lymphoid
tissues.
ADA estimation has been found to be useful in the diagnosis of
tuberculosis pleural effusion and ascites.
High ADA levels have also been reported in effusions due to
rheumatoid arthritis, lymphoma, chronic lymphatic leukaemia,
empyema, parapneumonic effusions, and mesothelioma.
ADA exists as two isoenzymes, ADA1 and ADA2, each with
unique biochemical properties.
The ADA1 isoenzyme is found in all cells with the highest
activity in lymphocytes and monocytes,
whereas ADA2 isoenzyme appears to be found only in
monocytes. In tuberculosis pleural effusion, ADA2 isoenzyme is
considered to be primarily responsible for total ADA activity,
while in parapneumonic effusions, the ADA1 isoenzyme is the
major isoenzyme of ADA. Thus, measurement of individual

Interferon-Y:
Interferon-y (IFN-y) is a cytokine produced by activated
T-lymphocytes. It plays a fundamental role in the
immune response to tuberculosis. High levels of IFN-y
have been reported in tuberculosis pleural effusions,
possibly related to in situ stimulation of CD4+ T
lymphocytes by tuberculosis antigens. A few studies
have shown a better sensitivity and specificity of pleural
IFN-y levels as compared to ADA levels.
Other non-conventional tests:
Lysozyme, a bacteriolytic protein which is widely
distributed in body fluids and many cells is a marker of
general inflammatory response. Lysozyme estimation
has been found to help identifying tuberculosis pleural
effusion.

Molecular methods:
Of these, polymerase chain reaction (PCR) has
often been applied to the CSF and pleural fluid to
detect various sequences representing the DNA of
M. tuberculosis.
Though the diagnostic utility of PCR in blood,
other body fluids such as ascitic fluid, urine,
pericardial fluid, pus from cold abscesses, and
tissue biopsy specimens has been studied,
available evidence is far from convincing. These
test results must be interpreted in the appropriate
clinical situation with caution.
PCR alone must not be the sole evidence on
which antituberculosis treatment is initiated or
withheld.

Xpert Test:
The recently developed CE-marked Xpert MTB/RIF
(Xpert)test (Cepheid Inc.), based on nested real-time
PCR and molecular beacon technology, has been
shown to be
1. rapid, with a result for TB and RIF resistance in
under 2 h;
2. not prone to cross-contamination;
3. requires minimal biosafety facilities;
4. can be performed by technicians with little training;
5. and has a high sensitivity in smear-negative
pulmonary TB (the last factor being particularly
relevant for patients with HIV infection).
. These characteristics also make it a potentially
attractive tool for extrapulmonary specimens.

Xpert sensitivity and specificity results were


assessed in comparison to a composite reference
standard made up of smear and culture results
and clinical, radiological, and histological
findings.
The sensitivity of the Xpert assay was 81%
(228/283 specimens) (64% [89/138] for smearnegative cases and 96% [139/145] for smearpositive cases), with a specificity of 99.6%.
The sensitivity was found to be high for the
majority of specimen types (63 to 100%) except
for cerebrospinal fluid, the sensitivity of which
was 29% (2/7 specimens). The Xpert test
correctly identified 98% of phenotypic rifampin
(RIF)-resistant cases and 94% of phenotypic RIFsusceptible cases.
Advantages overcome the higher cost of the
investigation.

Treatment
Part:

Category of TB patient for registration on diagnosis:


New
A patient who has definitely never taken anti-TB drugs or who
has taken anti-TB drugs for less than one month.
Relapse
A TB patient who:
a) previously received treatment and was declared cured or
b) treatment completed; and has once again developed
bacteriologically positive (by smear or culture) TB.
) Treatment after failure
) A patient who is started on a re-treatment regimen after having
failed
) previous treatment.
) Treatment after default
) A TB patient who returns to treatment, bacteriologically positive,
) following interruption of treatment for 2 months or more.

Some authorities recommend a 7


month continuation phase with daily
isoniazid and rifampicin (7HR) for
Category 1 patients with particular
forms of TB. These are TB meningitis,
miliary TB and spinal TB with
neurological signs.

Indications for treatment with


steroids:
* TB meningitis (decreased consciousness,
neurological defects, or spinal block).
* TB pericarditis (with effusion or constriction).
* TB pleural effusion (when large with severe
symptoms).
* Hypoadrenalism (TB of adrenal glands).
* TB laryngitis (with life-threatening airway
obstruction).
* Severe hypersensitivity reactions to anti-TB drugs.
* Renal tract TB (to prevent ureteric scarring).
* Massive lymph node enlargement with pressure
effects.

Recommended treatment doses of


prednisolone:
Rifampicin is a potent inducer of hepatic enzymes that
metabolize steroids. The effective dose of prednisolone
is therefore half the prescribed treatment dose given to
the patient.

Is steroid treatment safe in TB/HIV patients?

Steroids are immunosuppressants.


Steroids may further depress
immunity and increase risk of
opportunistic infections in HIVpositive patients. However, on
balance, TB/HIV patients are still
likely to benefit from the use of
steroids for the above indications.

Você também pode gostar